Forced Expression of Foxg1 in the Cortical Hem Leads to the Transformation of Cajal-Retzius Cells into Dentate Granule Neurons

Abstract

The Wnt- and BMP-rich cortical hem has been demonstrated to be critical for the pattern formation of the telencephalon, and it is particularly important for the induction of the hippocampus. Meanwhile, the cortical hem is one of the sources of Cajal-Retzius cells. Many Cajal-Retzius cells are produced in the hem and populated to the media-caudal surface of the telencephalon. However, the mechanism of the maintenance of the hem remain unclear. In this study, we generated a transgenic mouse line CAG-loxp-stop-loxp-Foxg1-IRES-EGFP. By crossing Fzd10CreERTM with this line, combined with tamoxifen induction, Foxg1 was ectopically expressed in the hem from embryonic day 10.5 (E10.5) onwards. We have found the hem-derived Cajal-Retzius cells were transformed into dentate granule neurons accompanied with ectopic expression of Lhx2. However, the morphology of the hem displayed no obvious changes. The hem specific markers, Wnt3a and Wnt2b, were slightly downregulated. Our results indicate that Foxg1 is sufficient to induce the expression of Lhx2 in the dorsal part of the hem. The ectopic Lhx2 and decreased Wnt signals may both contribute to the cell fate switch. Our study provides new insight into the mechanism underlying the maintenance of the hem.

Keywords

• cortical hem
• Cajal-Retzius cell
• cortical patterning
• Foxg1
• Lhx2
• hippocampus
• granule cell
• Wnt